1. Field of the Invention
The present invention relates to a novel bicyclic compound and a platelet aggregation inhibitor containing the same or a derivative of the same.
The platelet aggregation inhibitor of the invention is useful as a preventive or a remedy of thrombosis such as an ischemic cardiac disease, ischemic brain disease, peripheral circulatory impairment, arterial thrombus, arterial sclerosis and pulmonary vascular impairment, and also as a preventive or a remedy of restenosis or reocclusion after percutaneous transluminal coronary angioplasty or percutaneous transluminal coronary recanalization.
2. Description of Related Art
Various medicines for inhibiting aggregation of platelets have been used for the curing of thrombosis since the platelets were found to play an important role for a crysis of the thrombosis. The aggregation of platelets is induced by various stimuli such as ADP, collagen, epinephrine, thrombin, thromboxane A, and platelet activating factors. Therefore, anti-platelet drugs exhibit an inhibiting effect merely for the platelet aggregation caused by restricted kinds of stimulus and thus validity of these drugs is limited. On the other hand, the final step in the platelet aggregation process is a mutual combination of platelets by way of fibrinogen. The step is common and independent of the kind of aggregation eliciting stimulus. Consequently, in recent years, focused on an anti-platelet drug which directly inhibits the combination of platelets and fibrinogen. Such a drug inhibits the whole aggregation eliciting stimuli. It has been found that the binding site of fibrinogen for platelets is glycoprotein GP II b/III m a which is present in a platelet membrane and that the structure of -Arg-Gly-Asp- in a fibrinogen molecule has a minimum amino acid sequence which is required for combination with GP II b/III a. Many non-peptide compounds which are similar in structure to the straight chain or cyclic peptide compound having the amino acid sequence of -Arg-Gly-Asp- have been reported thereafter [Drug of the Future, 19(2), 135(1994) and 19(5), 461(1994)]. The common structure of the so far known non-peptide compounds has an acid group such as a carboxyl group which corresponds to a carboxyl group in aspartic acid and in a certain distance a basic group such as an amidino group, guanidino group, piperadinyl group and aminomethyl group which correspond to a guanidino group in arginine. Further, diversity has been found on the skeleton structure which connects the acid group with the basic group. WO 94/29273 has disclosed bicyclic compounds formed by condensation of two six-membered rings as the skeleton structure. However, WO 94/29273 has practically described only three compounds which have a tetrahydroisoquinoline structure. The inhibiting action of these compounds for human platelet aggregation is 1-13 .mu.M at IC.sub.50, and thus the activity is still unsatisfactory for an anti-platelet drug.